Kinetics of nasal epithelial cell loss and proliferation in F344 rats following a single exposure to 0.5 ppm ozone.

Repeated exposure to 0.5 ppm ozone (O3) induces mucous cell metaplasia in the nasal transitional epithelium (NTE) of rats. The cellular events which commit the NTE to undergo this phenotypic alteration occur during the first 3 days of exposure. To examine the kinetics of the early cellular responses of NTE to O3, F344 rats were exposed to filtered air or 0.5 ppm O3 for 8 hr and euthanized 2, 4, 6, 8, 12, 16, 20, 24, and 36 hr postexposure (PE). Two hours before euthanization, rats were injected with bromodeoxyuridine (BrdU) to label S-phase cells. The nasal cavities were fixed and processed for light microscopy. Sections from the anterior nasal cavity were immunostained to detect BrdU-labeled cells and analyzed to determine the numeric densities of NTE cells and intraepithelial neutrophils, and the labeling index (LI; [BrdU-labeled epithelial cells/total epithelial cells] x 100) and unit length labeling index (ULLI; BrdU-labeled epithelial cells/mm basal lamina) of the NTE overlying maxilloturbinates. O3 exposure induced a transient influx of neutrophils 2-4 hr PE and a significant (17%) loss of NTE cells 2-4 hr PE. An increase in epithelial DNA synthesis was first detected 12 hr PE. In this study, there was no difference in the sensitivity of the two measures of epithelial cell DNA synthesis. Both the LI and ULLI were greatest 20-24 hr PE and were reduced, but still greater than those of controls, by 36 hr PE. The numeric density of NTE cells returned to control levels 20-24 hr PE. This study has defined the kinetics of acute O3-induced NTE cell injury, loss, and proliferation in vivo. The transit time from Go to S, after O3-induced injury, was 12-20 hr and the duration of G2 + M was 8-12 hr. These data may be used to further explore the early cellular and molecular events that lead to ozone-induced mucous cell metaplasia.